Antimicrobial Pharmacophore Screening of Imidazole[1,2-a] Pyrazine Derivatives: A Quantitative Structure-Activity Relationship Approach
Abstract
An extensive computational analysis examines 10 new compounds with possible pharmacological properties. Absorption, distribution, metabolism, and excretion (ADME) projections indicated that all drugs exhibited good gastrointestinal absorption, albeit with varying solubility profiles and permeability across the blood-brain barrier. Utilising bioavailability radar analysis, the ideal physicochemical characteristics of many substances were determined. The results of structural similarity investigations indicated that certain compounds may have potential anticancer, anticonvulsant, antibacterial, antiulcer, antiviral, and anti-inflammatory properties. In the context of antibacterial action, Quantitative structure-activity relationship (QSAR) modelling has identified compound 8 as the most highly promising option. Through pharmacophore modelling and target prediction, Staphylococcus aureus Pyruvate carboxylase (SaPC) was identified as the most likely molecular target for chemical 8. The molecular docking experimental investigations of compound 8 with SaPC revealed a binding energy of -6.9 kcal/mol, accompanied by promising stability indications in a biological setting. The MMGBSA energy analysis demonstrated the significance of hydrophobic interactions, van der Waals forces, and hydrogen bonding in the mechanism of interaction. The results of this study provide valuable insights for enhancing and advancing the optimization and development of these chemicals, specifically compound 8, in the field of antimicrobial drug discovery that targets Staphylococcus aureus.